Brain injury is one of the complications in COVID-19 intensive care unit (ICU) survivors, though the precise underlying mechanism is unclear. It is likely caused by a combination of prolonged hypoxia, a massive systemic inflammatory response, direct infection of the brain and small vessel vasculitis in combination with widespread hypercoagulopathy and thrombosis. Using novel MRI techniques, blood-brain barrier (BBB) permeability, as well as other microstructural and microvascular properties of the brain tissue, will be assessed non-invasively in COVID-19 ICU survivors approximately one year after ICU admission and compared to serial clinical and laboratory measurements of hypercoagulation and inflammation during the (ICU) admission. This study aims to relate factors of hypercoagulability, inflammation or general illness itself (all during ICU admission) to microstructural and microvascular abnormalities on follow-up brain advanced 3T and 7T MRI in COVID-19 ICU survivors. In addition, neuropsychological tests and an objective smell/taste test will be used to evaluate neuropsychological status and sense of smell/taste. By gaining more insight into the pathogenesis of brain injury, the treatment of COVID-19 patients in the acute phase might be improved.

Brain injury is one of the complications in COVID-19 intensive care unit (ICU) survivors, though the precise underlying mechanism is unclear. It is likely caused by a combination of prolonged hypoxia, a massive systemic inflammatory response, direct infection of the brain and small vessel vasculitis in combination with widespread hypercoagulopathy and thrombosis. Using novel MRI techniques, blood-brain barrier (BBB) permeability, as well as other microstructural and microvascular properties of the brain tissue, will be assessed non-invasively in COVID-19 ICU survivors approximately 12-24 months after ICU admission and compared to serial clinical and laboratory measurements of hypercoagulation and inflammation during the (ICU) admission.

This study aims to relate factors of hypercoagulability, inflammation or general illness itself (all during ICU admission) to microstructural and microvascular abnormalities on follow-up brain advanced 3T and 7T MRI in COVID-19 ICU survivors. By gaining more insight into the pathogenesis of brain injury, the treatment of COVID-19 patients in the acute phase might be improved.

This is a mono-center follow-up cohort study with measurements at 12-24 months post hospital discharge. This study will include 70 adults who survived a severe COVID-19 infection for whom ICU admission was necessary during the second/third COVID wave (period October 2020- ongoing). These patients will be recruited from the MaastrICCht cohort from the Department of Intensive Care (MUMC+).

Patients will undergo an MRI scan (3T) and optionally a second MRI scan (7T) of approximately 60 minutes each. These scans will lead to insights in microstructural and microvascular abnormalities, BBB impairment, and in possible effects of a severe COVID-19 infection on the brainstem and the glymphatic system. In addition to the MRI measurements, blood samples will be drawn (approximately 20ml) to evaluate ICU follow-up levels of hypercoagulation and inflammation biomarkers. Follow-up short neuropsychological tests and two short questionnaires will be used to assess cognitive, neurological, olfaction and functional status. A brief objective smell and taste testing will be done to get an objective measure of sense of smell and taste.

By gaining more insight into the pathogenesis of brain injury, the treatment of COVID-19 patients in the acute phase might be improved.

Inclusion Criteria:

• Proven COVID-19 infection for which participant was admitted to the ICU for at least 3 days
• Included in the MaastrICCht cohort (a large database of serial measurements collected during ICU stay from patients with COVID-19 admitted to the ICU in the Maastricht University Medical Center+)
• Informed consent is given
• Sufficient command of the Dutch language to follow test instructions and understand the information letter, informed consent, and questionnaires

Exclusion Criteria:

• Objective cognitive impairments before hospital admission for the COVID-19 infection
• An unexpected incident leading to severe neurological damage after hospital discharge (such as stroke or traumatic brain injury)
• Contra-indications for MRI scanning (e.g. metal implants, cardiac pacemaker, claustrophobia, pregnancy, and tattoos in the head/neck region)
• Unwillingness to be informed about clinical relevant (abnormal) MRI-findings
• Contra-indications for a gadolinium-based MRI contrast agent (known allergy or insufficient kidney function determined by an eGFR < 30 mL/min)
• Physical inability to travel to one of the locations (e.g. bedridden patients)

The population consists of adult patients who survived a COVID-19 infection for which ICU hospital admission was necessary during the second/third pandemic wave (October 2020 - ongoing).